MARCH6-ERAD in hepatic lipid metabolism and MASLD
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
MARCH6-ERAD in hepatic lipid metabolism and MASLD SUMMARY The liver plays a pivotal role in lipid metabolism, and its dysregulation is central to the progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), including steatosis, fibrosis, and nonalcoholic steatohepatitis (NASH). The endoplasmic reticulum (ER) maintains lipid homeostasis, with sterol regulatory element-binding protein 1 (SREBP1) acting as a critical ER-resident transcription factor. Elevated SREBP1 levels drive lipogenesis and hepatic steatosis in MASLD, underscoring the need for tight regulation. While SREBP1 degradation is essential for lipid homeostasis, the mechanisms governing its turnover remain poorly understood. ER-associated protein degradation (ERAD) plays a crucial role in maintaining protein homeostasis, targeting both misfolded and functional proteins for degradation. Among ERAD-specific E3 ubiquitin ligases, MARCH6 is underexplored in the liver, representing a significant gap in understanding hepatic metabolism. Preliminary studies reveal that MARCH6 functions as a sterol sensor, modulating lipid homeostasis through SREBP1 ubiquitination and degradation. Loss of MARCH6 in hepatocytes results in excessive lipid accumulation, increased expression of lipogenic genes, and exacerbated MASLD progression. This research proposes that MARCH6-ERAD serves as a critical negative regulator of lipogenesis, counterbalancing the positive regulation by HRD1-ERAD. To test the hypothesis that MARCH6-ERAD regulates hepatic lipid homeostasis via SREBP1 ubiquitination and degradation, this study proposes two specific aims: Determine the functional significance of MARCH6-ERAD in maintaining lipid homeostasis and its role in MASLD. This aim will explore the responsiveness of MARCH6 to metabolic signals, establish its role as a regulator of lipid synthesis and uptake, and assess its therapeutic potential in MASLD (Aim 1). Establish the role of MARCH6-ERAD in regulating lipid metabolism through SREBP1 ubiquitination and degradation. This aim will confirm SREBP1 as a substrate of MARCH6, delineate the ubiquitination-degradation mechanism, and assess its impact on MASLD (Aim 2). This study will provide groundbreaking insights into the post-translational regulation of hepatic lipid metabolism, positioning MARCH6-ERAD as a sterol sensor and a critical factor in preventing MASLD progression. RELEVANCE TO HUMAN HEALTH: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a growing global health concern linked to obesity and diabetes. This study investigates the role of MARCH6-ERAD as a critical regulator of hepatic lipid metabolism, demonstrating its ability to modulate SREBP1 degradation and maintain lipid homeostasis. By uncovering MARCH6's therapeutic potential, this research aims to inform novel strategies to prevent or treat MASLD and improve patient outcomes.
Grant Summary
MARCH6-ERAD in hepatic lipid metabolism and MASLD is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $662K for university, nonprofit, healthcare org. Applications are due 2031-03-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $662K
2031-03-31
- 1Confirm your organization is eligible for MARCH6-ERAD in hepatic lipid metabolism and MASLD from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases before the deadline.
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MARCH6-ERAD in hepatic lipid metabolism and MASLD: Frequently Asked Questions
Who is eligible for the MARCH6-ERAD in hepatic lipid metabolism and MASLD?
MARCH6-ERAD in hepatic lipid metabolism and MASLD is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the MARCH6-ERAD in hepatic lipid metabolism and MASLD provide?
MARCH6-ERAD in hepatic lipid metabolism and MASLD provides up to $662K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the MARCH6-ERAD in hepatic lipid metabolism and MASLD deadline?
Applications for MARCH6-ERAD in hepatic lipid metabolism and MASLD are due 2031-03-31 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the MARCH6-ERAD in hepatic lipid metabolism and MASLD?
To apply for MARCH6-ERAD in hepatic lipid metabolism and MASLD, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.